scholarly journals From Bench to Bedside and Back Again

2016 ◽  
Vol 125 (3) ◽  
pp. 590-594 ◽  
Author(s):  
Mervyn Maze
Keyword(s):  
Adenosine Receptors ◽  
Adrenergic Receptors ◽  
Noradrenergic Neurons ◽  
Opiate Antagonist ◽  
Adrenergic Agonist ◽  
Before And After ◽  
Adenosine Antagonist ◽  
A1 Adenosine Receptors ◽  
Dose Dependent Increase ◽  
Dose Dependent

Abstract Dexmedetomidine Diminishes Halothane Anesthetic Requirements in Rats Through a Postsynaptic Alpha 2 Adrenergic Receptor. By Segal IS, Vickery RG, Walton JK, Doze VA, and Maze M. Anesthesiology 1988; 125:590–4. Abstract reprinted with permission. The effect of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole (medetomidine), the α2 adrenergic agonist, on anesthetic requirements was investigated in rats anesthetized with halothane. Halothane MAC was determined before and after either dexmedetomidine (d-enantiomer) or levomedetomidine (l-enantiomer) 10, 30, and 100 μg/kg, or vehicle intraperitoneally. There was a dose-dependent increase in MAC with the d-, but not the l-, stereoisomer. At the highest dose of dexmedetomidine (100 μg/kg), halothane could be discontinued for up to 30 min with no response to tail clamping. To determine whether α2 adrenoreceptors mediated this effect of dexmedetomidine on MAC, cohorts of rats were pretreated with idazoxan, 10 mg/kg intraperitoneally, a highly selective α2 antagonist. This completely prevented the reduction of MAC caused by dexmedetomidine. To determine whether the reduction of MAC caused by dexmedetomidine was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg intraperitoneally, an opiate antagonist, or 8-phenyltheophylline, 2.5 mg/kg intraperitoneally, an A1 adenosine antagonist. These two pretreatments did not alter the reduction of MAC by dexmedetomidine. To determine whether postsynaptic mechanisms mediate the anesthetic effect of dexmedetomidine, rats were depleted of central catecholamine stores with either n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine or reserpine and α-methyl-para-tyrosine, and MAC was determined before and after each dose of dexmedetomidine. While the catecholamine-depleted rats had a lower basal MAC than the vehicle controls, there was still a profound reduction in halothane MAC after administration of dexmedetomidine. The reduction of MAC by dexmedetomidine was blocked with idazoxan in the catecholamine-depleted rats. These data indicate that the reduction of MAC caused by dexmedetomidine is mediated through α2 adrenoreceptors with no apparent involvement of either opiate or A1 adenosine receptors. Data from catecholamine-depleted rats suggest that the mediating mechanism must involve site(s) other than or in addition to the presynaptic α2 adrenergic receptors on noradrenergic neurons. The authors conclude that central postsynaptic α2 adrenergic receptors mediate a significant part of the reduction of anesthetic requirements caused by dexmedetomidine.

Cardiac effects of injections of epinephrine into the spinal intermediolateral column

1993 ◽  
Vol 265 (2) ◽  
pp. H633-H641 ◽  
Author(s):  
V. K. Malhotra ◽  
A. Kachroo ◽  
H. N. Sapru
Keyword(s):  
Adrenergic Receptors ◽  
Cardiovascular Responses ◽  
Spinal Level ◽  
Cardiac Effects ◽  
Alpha Adrenergic Receptors ◽  
Small Doses ◽  
The Right ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Stimulation Of

Small doses of epinephrine (0.008, 0.05, and 0.1 pmol, i.e., 20-nl volumes of 0.40, 2.5, and 5 microM solutions) produced a dose-dependent increase in heart rate when micro-injected into the right intermediolateral column (IML) at T2 spinal level. These effects were mediated via alpha 1-adrenergic receptors because prazosin blocked them. The presence of alpha 1-adrenergic receptors at this site was confirmed by microinjections of phenylephrine (a specific agonist for these receptors); phenylephrine elicited tachycardia. Larger doses of epinephrine (320, 2,000, and 3,200 pmol, i.e., 20-nl volumes of 16, 100, and 160 mM solutions) caused bradycardia when microinjected into the IML. These effects were mediated via alpha 2-adrenergic receptors because idazoxan blocked them. The presence of alpha 2-adrenergic receptors at this site was confirmed by microinjections of clonidine (a specific agonist for these receptors); clonidine elicited bradycardia. Injections of the vehicle (20 nl of normal saline containing 0.3% ascorbic acid, pH 7.4) did not evoke a response. Epinephrine, prazosin, or idazoxan did not alter the responses to L-glutamate. None of the doses of epinephrine elicited any response when injected intravenously. The aforementioned results provide pharmacological evidence for the presence of alpha 1- and alpha 2-adrenergic receptors in the IML at T2. Thus a basis is provided for investigating the role, if any, of alpha-adrenergic receptors in the IML in mediating cardiovascular responses elicited by the stimulation of different brain stem areas.

scholarly journals Stimulation of NTS A1 adenosine receptors differentially resets baroreflex control of regional sympathetic outputs

2008 ◽  
Vol 294 (1) ◽  
pp. H172-H182 ◽  
Author(s):  
Tadeusz J. Scislo ◽  
Tomoko K. Ichinose ◽  
Donal S. O'Leary
Keyword(s):  
Adenosine Receptors ◽  
Dependent Manner ◽  
Glutamatergic Transmission ◽  
Sprague Dawley ◽  
Response Curves ◽  
Baroreflex Control ◽  
Adenosine Receptor Agonist ◽  
Before And After ◽  
Dose Dependent ◽  
Stimulation Of

Previously we showed that pressor and differential regional sympathoexcitatory responses (adrenal > renal ≥ lumbar) evoked by stimulation of A1 adenosine receptors located in the nucleus of the solitary tract (NTS) were attenuated/abolished by baroreceptor denervation or blockade of glutamatergic transmission in the NTS, suggesting A1 receptor-elicited inhibition of glutamatergic transmission in baroreflex pathways. Therefore we tested the hypothesis that stimulation of NTS A1 adenosine receptors differentially inhibits/resets baroreflex responses of preganglionic adrenal (pre-ASNA), renal (RSNA), and lumbar (LSNA) sympathetic nerve activity. In urethane-chloralose-anesthetized male Sprague-Dawley rats ( n = 65) we compared baroreflex-response curves (iv nitroprusside and phenylephrine) evoked before and after bilateral microinjections into the NTS of A1 adenosine receptor agonist ( N6-cyclopentyladenosine, CPA; 0.033–330 pmol/50 nl). CPA evoked typical dose-dependent pressor and differential sympathoexcitatory responses and similarly shifted baroreflex curves for pre-ASNA, RSNA, and LSNA toward higher mean arterial pressure (MAP) in a dose-dependent manner; the maximal shifts were 52.6 ± 2.8, 48.0 ± 3.6, and 56.8 ± 6.7 mmHg for pre-ASNA, RSNA, and LSNA, respectively. These shifts were not a result of simple baroreceptor resetting because they were two to three times greater than respective increases in baseline MAP evoked by CPA. Baroreflex curves for pre-ASNA were additionally shifted upward: the maximal increases of upper and lower plateaus were 41.8 ± 16.4% and 45.3 ± 8.7%, respectively. Maximal gain (%/mmHg) measured before vs. after CPA increased for pre-ASNA (3.0 ± 0.6 vs. 4.9 ± 1.3), decreased for RSNA (4.1 ± 0.6 vs. 2.3 ± 0.3), and remained unaltered for LSNA (2.1 ± 0.2 vs. 2.0 ± 0.1). Vehicle control did not alter the baroreflex curves. We conclude that the activation of NTS A1 adenosine receptors differentially inhibits/resets baroreflex control of regional sympathetic outputs.

Neonatal testosterone potentiates stimulated prolactin secretion in adult oestrogen-primed rats

1986 ◽  
Vol 109 (1) ◽  
pp. 57-60 ◽  
Author(s):  
R. G. Dyer ◽  
S. Mansfield
Keyword(s):  
Testosterone Propionate ◽  
Prolactin Secretion ◽  
Female Rats ◽  
Neonatal Exposure ◽  
Adult Rats ◽  
Blood Samples ◽  
Before And After ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Stimulation Of

ABSTRACT Blood samples were collected from oestrogen-primed gonadectomized adult rats before and after electrical stimulation of the preoptic part of the hypothalamus. Six groups of rats were used for the experiments. These were (a) males castrated on the first day of life, (b) males castrated after puberty, (c) females ovariectomized after puberty and (d), (e) and (f) females given testosterone propionate at birth (1·25, 0·125 and 0·0125 mg/rat respectively). Neonatal exposure of the female rats to testosterone caused a dose-dependent increase in the amounts of prolactin released to levels significantly (P<0·01) higher than those observed in male animals and in untreated females. The results indicate that although neonatal testosterone inhibits oestrogen-stimulated prolactin secretion in adult rats, the neuroendocrine apparatus controlling secretion of the hormone is capable of being activated to greater effect after exposure to androgens at the time of birth. J. Endocr. (1986) 109, 57–60

Activation of α2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men

2003 ◽  
Vol 285 (3) ◽  
pp. E599-E607 ◽  
Author(s):  
Vladimir Stich ◽  
Tereza Pelikanova ◽  
Petr Wohl ◽  
Coralie Sengenès ◽  
Alexia Zakaroff-Girard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adrenergic Receptors ◽  
Glycerol Concentration ◽  
Time Intervals ◽  
Subcutaneous Abdominal Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Male Subjects

The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic α2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 ± 0.9 yr; body mass index: 23.8 ± 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 μM) or epinephrine (1 and 10 μM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 μM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 μM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 μM phentolamine (a nonselective α-AR antagonist), the inhibition of epinephrine (10 μM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the β-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by α2-ARs.

scholarly journals Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo- controlled, randomized phase Ib study

Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2347-2353 ◽  
Author(s):  
V D'Hondt ◽  
Y Humblet ◽  
T Guillaume ◽  
S Baatout ◽  
C Chatelain ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
C Reactive Protein ◽  
Platelet Recovery ◽  
Phase Ib ◽  
Reactive Protein ◽  
Before And After ◽  
Systemic Symptoms ◽  
Dose Levels ◽  
Dose Dependent Increase ◽  
Dose Dependent

Recombinant human interleukin-6 (IL-6) has previously been shown to increase platelet counts in normal and sublethally irradiated mice, dogs, and primates. To assess its tolerance and efficacy in clinical use, we performed a randomized phase Ib study in patients with ovarian carcinoma. IL-6 was administered during an initial 7-day cycle before any chemotherapy. Beginning 7 days later, six cycles of chemotherapy containing carboplatin were administered every 3 weeks. During chemotherapy cycles 2 to 6, IL-6 was administered from day 4 through day 17 at escalating dose levels from 0.5 to 10 micrograms/kg/d. At each level, three patients received IL-6 and one patient received a placebo. During the prechemotherapy cycle of IL-6, a dose-dependent increase in platelet count was observed from day 12 to 15 and was maximal on day 15 (r = .77; P < .01). The median ploidy of bone marrow megakaryocytes shifted from 16 N to 32 N after 7 days of the initial prechemotherapy IL-6 administration. Dose-dependent increases in C-reactive protein (CRP) and fibrinogen levels were observed on day 8 (P < .0001 for both). A significant decrease in hemoglobin level occured rapidly after initiation of IL-6 therapy and was maximal on day 8 (P < .001). When given after chemotherapy, IL-6 accelerated platelet recovery after chemotherapy cycles 2 to 6. Postponements of scheduled chemotherapy due to thrombocytopenia were less frequent in patients treated with IL-6. No difference in either neutrophils or peripheral blood progenitor assays was observed during or after IL-6 treatment. Toxicity of IL-6 appeared mild and was not dose-limiting up to 10 micrograms/kg/d. Systemic symptoms such as fever, headache, and myalgia were the main side effects and were easily relieved by acetaminophen administration. No biologic toxicity was observed. The data indicate that IL-6 is a well-tolerated cytokine and capable of accelerating platelet recovery in patients receiving chemotherapy.

Interaction of β-adrenergic agonists and antagonists with the stimulation of growth hormone release induced by clonidine or by morphine in the rat

1982 ◽  
Vol 94 (3) ◽  
pp. 327-331 ◽  
Author(s):  
M. T. Bluet-Pajot ◽  
D. Durand ◽  
F. Mounier ◽  
C. Schaub ◽  
C. Kordon
Keyword(s):  
Adrenergic Receptors ◽  
Hormone Release ◽  
Adrenergic Agonists ◽  
Adrenergic Agonist ◽  
Basal Secretion ◽  
Experimental Conditions ◽  
Gamma Hydroxybutyrate ◽  
Β Adrenergic Receptors ◽  
Dose Dependent

The β-adrenergic agonist, isoprenaline, and antagonist, propranolol, had no effect on the delayed basal secretion of GH consistently observed in rats treated with the narco-analgesic gamma-hydroxybutyrate. Under the same experimental conditions, GH release was distinctly stimulated by infusion of the α-adrenergic agonist, clonidine, and by morphine; both responses were dose-dependent. The effects of β-adrenergic agonists and antagonists on these GH responses were as follows: in rats pretreated with isoprenaline the GH release induced by clonidine and morphine was abolished whereas it was enhanced in rats pretreated with propranolol. These data confirmed and extended previous reports from this laboratory on the inhibitory role of β-adrenergic receptors on GH regulation.

Prostanoid inhibition potentiates vasoconstrictor response to acetylcholine in dog lung

1986 ◽  
Vol 61 (3) ◽  
pp. 1035-1040 ◽  
Author(s):  
J. D. Catravas ◽  
W. F. Hofman ◽  
I. C. Ehrhart
Keyword(s):  
Pressor Response ◽  
Phosphodiesterase Inhibitor ◽  
Left Lobe ◽  
Vasoconstrictor Response ◽  
Lower Left Lobe ◽  
Before And After ◽  
Muscarinic Cholinoceptors ◽  
Pulmonary Arterial ◽  
Dose Dependent Increase ◽  
Dose Dependent

We determined whether cyclooxygenase or phosphodiesterase inhibition would alter the vasomotor response to acetylcholine in the dog lung. Lower left lobes were removed and then cannulated, ventilated, and pump perfused with autogenous blood at constant flow [6.0 +/- 0.1 ml X min-1 X g-1 lower left lobe (LLL)]. LLLs were challenged with graded doses of acetylcholine (ACh) (100–1,000 nmol) into the arterial cannula before and after administration of either 40 microM indomethacin (n = 5), 1 mM aspirin (n = 4), or 1 mM theophylline (n = 5). ACh produced a dose-dependent increase in pulmonary arterial pressure (Pa) and a decrease in the upstream-to-down-stream resistance ratio (Rus/Rds). Pretreatment with either indomethacin or aspirin potentiated the Pa response to ACh while eliminating the ACh-associated decrease in Rus/Rds. Pretreatment with the phosphodiesterase inhibitor theophylline significantly antagonized the ACh pressor response and decrease in the Rus/Rds. The present study suggests that the pulmonary pressor response to ACh is enhanced with cyclooxygenase inhibition. Our results indicate that ACh stimulates pulmonary vascular muscarinic cholinoceptors to cause vasoconstriction. Additionally or as sequelae to this response, predominantly vasodilatory prostanoids appear to be released.

scholarly journals Expression of adrenergic receptors in mouse preimplantation embryos and ovulated oocytes

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1139-1147 ◽  
Author(s):  
Štefan Čikoš ◽  
Pavol Rehák ◽  
Soňa Czikková ◽  
Jarmila Veselá ◽  
Juraj Koppel
Keyword(s):  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Cell Number ◽  
Embryo Cell ◽  
Preimplantation Embryos ◽  
Adrenergic Agonist ◽  
And Migration ◽  
Β Adrenergic Receptors ◽  
Dose Dependent ◽  
Receptor Family

Epinephrine and norepinephrine can play an important role in basic developmental processes such as embryogenesis and morphogenesis, regulating cell proliferation, differentiation and migration. We showed that β-adrenergic receptors can mediate the effects of catecholamines on preimplantation embryos in our previous work. In the present study, we designed specific oligonucleotide primers which can distinguish among all members of the α-adrenergic receptor family, and showed (using RT-PCR) that the α2C-adrenergic receptor is transcribed in ovulated oocytes, 8- to 16-cell morulae and expanded blastocysts. We did not detect the α2C-adrenoceptor transcript in 4-cell embryos. Our immunohistochemical study showed the presence of α-2C-adrenoceptor protein in ovulated oocytes, 8- to 16- cell embryos and blastocysts, but the signal in 4-cell embryos was weak, and probably represents remaining protein of maternal origin. We did not detect any other α-adrenergic receptor in preimplantation embryos and oocytes. Exposure of mouse preimplantation embryos to the α2-adrenergic agonist UK 14 304 led to significant reduction of the embryo cell number, and the effect was dose dependent. Our results suggest that epinephrine and norepinephrine could affect the embryo development in the oviduct via adrenergic receptors directly and support the opinion that maternal stress can influence the embryo even in very early pregnancy.

scholarly journals Activation of NTS A1adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex

2012 ◽  
Vol 303 (5) ◽  
pp. R539-R550 ◽  
Author(s):  
Tomoko K. Ichinose ◽  
Zeljka Minic ◽  
Cailian Li ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Adenosine Receptors ◽  
Right Atrial ◽  
Volume Control ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Severe Hypotension ◽  
Before And After ◽  
Sympathetic Responses ◽  
Dose Dependent

Previously we have shown that adenosine operating via the A1receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A1receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats ( n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT3receptor agonist phenylbiguanide, PBG, 1–8 μg/kg) before and after selective stimulation of NTS A1adenosine receptors [microinjections of N6-cyclopentyl adenosine (CPA), 0.033–330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control ( n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-( p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) ( n = 9) did not affect the reflex responses. We conclude that activation of NTS A1adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A1adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes integrated in the NTS.

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists

1998 ◽  
Vol 84 (1) ◽  
pp. 215-221 ◽  
Author(s):  
Paula Carvalho ◽  
Shane R. Johnson ◽  
Nirmal B. Charan
Keyword(s):  
Systemic Arterial Pressure ◽  
No Synthase ◽  
Dependent Manner ◽  
Routes Of Administration ◽  
Before And After ◽  
Endogenous Nitric Oxide ◽  
Baseline Values ◽  
Synthase Inhibitor ◽  
Dose Dependent Increase ◽  
Dose Dependent

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled β-agonists. J. Appl. Physiol. 84(1): 215–221, 1998.—We studied the dose-dependent effects of inhaled isoetharine HCl, a β-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Q˙br) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Q˙br. With a total dose of 17.5 mg, Q˙br increased from baseline values of 22 ± 3.4 (SE) to 60 ± 16 ml/min ( P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects β-agonist-induced increases in Q˙br, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). Intravenous l-NAME (30 mg/kg) rapidly decreased Q˙br by ∼80% of baseline, whereas l-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (∼22%) decrease. Pretreatment with l-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Q˙br in a dose-dependent manner and that β-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.

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